This invention relates to processes for the microbiological conversion of sterol derivatives to 5-androsten-17-one derivatives and their use.
It is known in the prior art that numerous microorganisms, such as, for example, those of the genera Arthrobacter, Brevibacterium, Microbacterium, Protaminobacter, Bacillus, Norcardia, Streptomyces, and especially Mycobacterium, have the natural ability to degrade zoosterols and phytosterols to carbon dioxide and water, with 4-androstene-3,17-dione and 1,4-androstadiene-3,17-dione are formed as intermediates.
Since numerous zoosterols and phytosterols, e.g., cholesterol, stigmasterol, capesterol, brassicasterol, and the sitosterols, are widely found in nature and thus are readily accessible raw materials for the synthesis of pharmacologically effective steroids, numerous investigations have been conducted to control the degradation of the sterols during fermentation so that further degradation of the thus-formed 4-androstene-3,17-dione and 1,4-androstadiene-3,17-dione is prevented.
For example, it is possible to prevent the further degradation of 1,4-androstadiene-3,17-dione and 4-androstene-3,17-dione by adding inhibitors to the fermentation batches. See Federal Republic of Germany Unexamined Laid-Open Applications DOS's Nos. 1,543,269 and 1,593,327 and U.S. Pat. No. 1,208,078. However, the use of such inhibitors makes these reactions very expensive on a commercial scale because, inter alia, the inhibitors employed must be removed from the fermentation cultures after the reaction has been accomplished to avoid discharging them into the waste water. Moreover, these conventional reactions have the disadvantage that they always produce 1,4-androstadiene-3,17-dione, alone or as a mixture with 4-androstene-3,17-dione and 1,4-androstadiene-3,17-dione is a poor starting material for the synthesis of numerous pharmacologically active steroids.
The further degradation of 1,4-androstadiene-3,17-dione and of 4-androstene-3,17-dione can also be prevented by using mutated microorganisms of the genus Mycobacterium for the fermentative conversion of the sterols. See U.S. Pat. No. 3,684,657. These mutants, however, have the disadvantage that they have a very limited capability for producing 1,4-androstadiene-3,17-dione or 4-androstene-3,17-dione from sterols.
It is an object of this invention to provide a process for the side chain degradation of sterols which does not have the disadvantages of known methods. Another object is the provision of a process for the cleavage of the 3-ethers. Other objects will be apparent to those skilled in the art.